197 Attention Regulation in Narcolepsy Type 1 Introduction Narcolepsy type 1 is a severely disabling neurological condition caused by a selective loss of hypocretin-producing neurons in the lateral and posterior hypothalamus [44, 45]. It is characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. People with narcolepsy type 1 also frequently report vigilance (also called “sustained attention” or “tonic alertness”) deficits, considered to be a result of EDS [94, 273, 274]. The ability to remain vigilant is essential for effective daytime functioning [275, 276]. People with narcolepsy therefore often report difficulties with studying or working, and are more frequently involved in traffic accidents [277-279]. Here, we report on a functional MRI (fMRI) study investigating the neurobiological basis of the vigilance difficulties in people with narcolepsy type 1 using the sustained attention to response task (SART). The neural correlates of vigilance regulation in general, different stages of attention and response inhibition capacities were studied. Various, often lengthy, tasks have been used to investigate vigilance in people with narcolepsy. First described by Robertson et al. (1997), the SART is a relatively short “Go/No-Go” task requiring continuous decision making depending on the repetitive presentation of visual stimuli [280]. These stimuli include single digits (1–9) that are transiently presented in a pseudorandom order with relatively sparse No-Go trials. The participant is instructed to respond with a button press, unless a “3” is being shown. Performing the task requires both sustained attention and executive functioning (including response inhibition) and has previously been validated for assessing everyday cognitive slips in people with narcolepsy and healthy controls [6, 93, 281]. Previous behavioural SART research in people with narcolepsy type 1 has revealed significantly worse test performance and longer reaction times than in healthy controls [6, 93, 281]. No study has yet focused on the neural substrates of attention regulation in narcolepsy type 1. Variable SART paradigms have been used in an MRI environment in healthy individuals, mainly differing in length and the makeup of the baseline condition. There is evidence that the SART induces task-positive cinguloopercular, frontoparietal, and supplementary motor cortex activation in healthy participants [282-285]. However, it remains unknown how changes in vigilance demand, different stages of attention and errors are processed in the brain. In this study, we tested the feasibility of a multilevel SART paradigm with increasing vigilance demand over two difficulty levels of moderate and higher difficulty in healthy participants and in individuals with narcolepsy type 1. 7
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